Method and system for monitoring internal electrical impedance of a biological object

ABSTRACT

Method and system for monitoring an internal electrical impedance of a biological object including Internal Thoracic Impedance (ITI) comprising placing two arrays of electrodes on opposite sides of the biological object, wherein each of said two arrays comprise three equally spaced electrodes; imposing an alternating electrical current between pairs of the electrodes and obtaining voltage signals representative of a voltage drop thereon, calculating two values of internal electrical impedance of the biological object corresponding to the uttermost electrodes of said two arrays of electrodes placed on the opposite sides of the biological object.

TECHNOLOGICAL FIELD AND BACKGROUND

The present invention relates to noninvasive biological metrologytechniques and, more particularly, to a method and device for measuringand/or monitoring an internal electrical impedance of a portion of abiological object, such as the lung(s) or the brain.

Fluid buildup in biological object is associated with many diseases,notably diseases of the heart. An important example of fluid buildupassociated with heart disease is acute congestion or edema of the lungs.Because these fluids usually have better electric conductivity thansurrounding tissues, changes in liquids volume can be detected by thetechnique of impedance plethysmography, based on measurements ofelectrical impedance of whole body or organ of interest.

Clinical signs of pulmonary edema (PED) are appeared on physicalexamination only after significant lung fluid accumulation and thereforeare not sufficiently sensitive to allow clinical monitoring of HeartFailure patients. A decrease in lung impedance (LI) reflects an increasein lung fluid content and may herald evolving PED at very early stageand indicate the need to initiate pre-emptive therapy.

The monitoring of liquid changes within a biological object using twoelectrodes, one either side of the biological object, is well known inthe art. However, this method has proved to be unfit for prolongedmonitoring due to the drift of skin-to-electrode contact layerresistance. During prolonged contact between electrode and skin“skin-electrode” impedance is changed as a result of electrolytepenetration to zone of contact and as a result common impedance betweentwo electrodes on both sides of the chest is also changed. In suchsituation change in common impedance is indicative mainly of variationof “skin-electrode” impedance and not or only in small proportionchanges in impedance of internal part of biological object or itsportion as for example lung impedance or brain impedance.

A method for overcoming this problem was developed by Kubicek et al.(Annals of the New York Academy of Sciences, 1970, 170(2):724-32; U.S.Pat. No. 3,340,867, reissued as Re. 30,101). Related U.S. patentsinclude Asrican (U.S. Pat. No. 3,874,368), Smith (U.S. Pat. No.3,971,365), Matsuo (U.S. Pat. No. 4,116,231) and Itoh (U.S. Pat. No.4,269,195). The method of Kubicek et al. uses a tetra-polar electrodesystem whereby the outer electrodes establish a current field throughthe chest. The inner voltage pickup electrodes are placed as accuratelyas is clinically possible at the base of the neck and at the level ofthe diaphragm. This method regards the entire portion of the chestbetween the electrodes as a solid cylinder with uniform parallel currentfields passing through it. However, because this system measures theimpedance of the entire chest, and because a large part of theelectrical field is concentrated in the surface tissues and aorta, thismethod is not sufficiently specific for measuring variation of liquidlevels in the lungs and has low sensitivity: 50 ml per Kg of body weight(Y. R. Berman, W. L. Schutz, Archives of Surgery, 1971. V. 102:61-64).It should be noted that such sensitivity has proved to be insufficientfor obtaining a significant difference between impedance values inpatients without pulmonary edema to those with an edema of averageseverity (A. Fein et al., Circulation, 1979, 60 (5):1156-60). In theirreport on the conference in 1979 concerning measuring the change in theamount of liquid in the lungs (Critical Care Medicine, 1980,8(12):752-9), N. C. Staub and J. C. Hogg summarize the discussion on thereports concerning the reports on the method of Kubicek et al. formeasuring thoracic bio-impedance. They conclude that the boundaries ofthe normal values are too wide, and the sensitivity of the method islower than the possibilities of clinical observation and radiologicalanalysis, even when the edema is considered to be severe. It isindicative that, in a paper six years later by N. C. Staub (Chest. 1986,90 (4):588-94), this method is not mentioned at all.

Another method for measuring liquid volume in the lungs is the focusingelectrode bridge method of Severinghaus (U.S. Pat. No. 3,750,649). Thismethod uses two electrodes located either side of the thorax, on theleft and right axillary regions. Severinghaus believed that part of theelectrical field was concentrated in surface tissues around the thoraxand therefore designed special electrodes to focus the field through thethorax. This method does not solve the problems associated with thedrift in the skin-to-electrode resistance described above. An additionalproblem is the cumbersome nature of the large electrodes required. Areview by M. Miniati et al. (Critical Care Medicine, 1987, 15(12):1146-54) characterizes both the method of Kubicek et al. and themethod of Severinghaus as “insufficiently sensitive, accurate, andreproducible to be used successfully in the clinical setting” (p. 1146).

Other notable recent work in measuring the impedance of a portion of thebody includes the tomographic methods and apparatuses of Bai et al.(U.S. Pat. No. 4,486,835) and Zadehkoochak et al. (U.S. Pat. No.5,465,730). In the form described, however, tomographic methods arebased on relatively instantaneous measurements, and therefore are notaffected by electrode drift. If tomographic methods were to be used forlong-term monitoring of pulmonary edema, they would be as subject toproblems of skin-to-electrode impedance drift as the other prior artmethods.

FIG. 1 schematically illustrates components of Transthoracic Impedance(TTI) with depiction of the thoracic cross-section. Measurementelectrodes 3 and 3′ are placed on opposite sides of the thorax of apatient. Transthoracic impedance (TTI) 2 generally composed by threecomponents: Internal Thoracic Impedance (ITI) 1 that nearly equalsinherent lung impedance (LI) plus high skin-electrode impedances at thefront 3 and at the back of the chest 3′. Internal Thoracic Impedance ofpatients without congestion (normal state) is relatively low 25-120Ω(mean 60Ω) that could be decreased by 15-50% with the development ofpulmonary congestion or edema. The skin-electrode impedance isrelatively high (200-800Ω) and its value could change as a result ofslow variations in skin ionic balance throughout monitoring of severalhours' duration. It is also depended from individual characteristics ofpatients such as skin consistent, weight, height and sex. The absolutevalues of TTI are typically between 450-1700Ω. The magnitude of ITIdecreasing during pulmonary congestion or edema development isapproximately 15-50% from normal baseline level (25-120Ω). It means thatITI decreases by 4-60Ω during pulmonary congestion or edema development.Obviously, this change in ITI represents only a small part (1-4%) of thehigh TTI and is, therefore, barely measurable.

In order to improve sensitivity of ITI measurements was proposed atechnique which enables to calculate skin-electrode impedance and it'svariations during measurements. Subtracting calculated skin-electrodeimpedance value from transthoracic impedance TTI provides a solution fora problem of skin-electrode impedance drift and significantly improvessensitivity of ITI measurement.

Such technique disclosed in Rabinovich et al in U.S. Pat. No. 5,749,369using multi-electrode system for impedance plethysmography with relativeimmunity to skin-electrode contact resistance drift. The technique usesmultiple electrodes defining one measurement and six (plurality)reference electrical circuits. Electrical impedances of all circuits aremeasured and internal impedance of the biological object is calculatedtherefrom based on some physical assumptions.

The Edema Guard Monitor (EGM) model RS-207 (RS Medical Monitoring,Israel) was developed according to the U.S. Pat. No. 5,749,369 toaddress the skin-electrode contact resistance drift monitoring problems.It is designed to noninvasively monitor with better signal-to-noisecharacteristics than other noninvasive devices.

This system solved the problems of high skin-to-electrode impedances andtheir drifts during prolonged monitoring by separating ITI from TTI byreducing skin-electrode impedance at the time of each ITI measurement.

The calculated ITI values based on noninvasive measurements therebycorrespond to ITI's measurements as if they were performed invasivelyvia electrodes placed within the thorax.

It also known that appropriate location of EGM's electrodes couldprovide passing electric-magnetic signal outside large arteries andmainly through the lungs' area (as illustrated in FIG. 1 ). However,lung also contains various heterogeneous structures such a middle sizearteries, veins or bronchi and also could contain pulmonary bullae,pulmonary cysts, etc. Such structures usually have differentconductivity from surrounding lung tissue.

According to the known noninvasive plethysmography approaches, includingEGM's approach, measured values of internal thoracic impedance (ITI)could be affected by the above-mentioned non-uniformities and will notbe accurate enough to be sensitive to small ITI (LI) variations.

There is accordingly a need in the art for a novel approach fornoninvasive technique solving the problem of limitedaccuracy/sensitivity to detect small ITI changes occurring during theearly stage of interstitial Edema when preventive treatment is desirableand most effective.

GENERAL DESCRIPTION

Thus, according to one broad aspect of the invention, there is provideda method for monitoring an internal electrical impedance of a biologicalobject, comprising placing two arrays of electrodes on opposite sides ofthe biological object, wherein each of said two arrays comprise threeequally spaced electrodes; imposing an alternating electrical currentbetween pairs of said electrodes and obtaining voltage signalsrepresentative of a voltage drop thereon, and calculating two values ofinternal electrical impedance of the biological object corresponding tothe uttermost electrodes of said two arrays of electrodes placed on theopposite sides of the biological object.

More specifically, the present invention is useful for monitoringInternal Thoracic Impedance (ITI).

In some embodiments calculated values of internal electrical impedancecould be compared therebetween and further could be denied or anaccepted based on the comparison result.

Preferably alternating electrical current with frequency from 50 to 200KHz and having a value from 0.5 to 5 mA could be used. More specificallyvalue from 1 to 2 mA is useful for measurements of Internal ThoracicImpedance (ITI).

According to yet another broad aspect of the invention, there isprovided a system for monitoring an internal electrical impedance of abiological object, comprising a plurality of electrodes, current sourceand a voltage measurement unit connected to an analog multiplexeroperable for alternately connecting said current source and said voltagemeasurement unit to form predetermined sets of said electrodes, acontrol unit with data processing utility for carrying out calculationsand comparing of calculated values of internal impedance.

In some embodiments system for monitoring internal electrical impedancecomprises six electrodes and a number of predetermined sets of theelectrodes is defined by number of combinations by pairs of theelectrodes.

More specifically, the present invention is useful as a medicalmonitoring system that comprising an impedance plethysmography device,with a plurality of electrodes, current source and a voltage measurementunit connected to an analog multiplexer operable for alternatelyconnecting said current source and the voltage measurement unit to formpredetermined sets of said electrodes, a control unit with dataprocessing utility for carrying out calculations and comparing ofcalculated values of internal impedance. More specifically, currentsource of the system provides alternating electrical current from 0.5 to5 mA with a frequency from 50 to 200 KHz.

Plurality of electrodes preferably includes six electrodes and a numberof predetermined sets of the electrodes is defined by number ofcombinations by pairs of the electrodes.

BRIEF DESCRIPTION OF THE DRAWINGS

In order to better understand the subject matter that is disclosedherein and to exemplify how it may be carried out in practice,embodiments will now be described, by way of non-limiting example only,with reference to the accompanying drawings, in which:

FIG. 1 illustrates components of Transthoracic Impedance (TTI) withdepiction of the thoracic cross-section.

FIG. 2 is a schematic illustration of two arrays of electrodes ofimpedance plethysmography device used to monitor pulmonary edema;

FIG. 3 is a partial schematic illustration of device according to onepreferred embodiment

FIG. 4A-4B schematically illustrates electric circuitry composed byplethysmography device electrodes and biological object (skin/lung)according to one preferred embodiment of the present invention;

FIG. 5 schematically illustrates electric circuitry composed byplethysmography device electrodes and biological object (skin/lung)according to another preferred embodiment of the present invention, and

FIG. 6 is a schematic block diagram of the system according to thepresent invention

DETAILED DESCRIPTION OF EMBODIMENTS

Reference is made to FIGS. 2 and 3 exemplifying the main principles ofthe invention.

As shown in FIGS. 2 and 3 two arrays of electrodes 101-103 and 104-106of a system 100 for measuring internal electrical impedance are placedon opposite sides of biological object 108. An analog multiplexer 110controlled by control unit CU performs selective connecting electrodes101-106 to a current source 112 and a voltage measurement unit 114.Selective connecting of electrodes 101-106 could form pre-determinedsets of electrodes comprising desired number of electrodes of any one orboth arrays of electrodes.

Sets formed by electrodes placed on the same side of biological object108 i.e. 101-103 or 104-106 forms “reference” circuits and sets formedby at least two electrodes of different group's forms measurementcircuits. It should be noted that pre-determined sets of electrodescomprise at least two electrodes. Analog multiplexer 110 is capable toconnect any desired combinations of electrodes 101-106 formingpre-determined sets.

Preferably each array comprises three equally spaced electrodes and areplaced on opposite sides of the biological object, e.g. opposite sidesof the thorax of a patient in case of impedance plethysmography (asillustrated specifically in FIG. 2 ).

Current source 112 supplies alternative electrical current ofsubstantially identical intensity, e.g. of about 0.5-5 mA betweenelectrodes of any predetermined set.

For impedance plethysmography preferably, current from about 1 mA toabout 2 mA at a frequency of between about 50 KHz and about 200 KHz isused. Current of about 1 mA most preferably could be used. The term“frequency”, as used herein, refers to the fundamental frequency of aperiodic waveform, so that the scope of the present invention includesalternating current of any periodic waveform, for example square, saw,etc. waves, and not just sinusoidal alternating current.

A voltage drop V across the measurement and reference circuits ismeasured by voltage measurement unit 114 while imposing an alternativecurrent between circuit's electrodes. Generally, voltage drop across themeasurement circuits being indicative of (proportional) a totalimpedance of the biological object and voltage drop across the referencecircuits being indicative of (proportional) skin-electrode impedance.

The inventors have found that for improving impedance plethysmographyall possible sets each including only pair of electrodes (forming bothmeasurement and reference circuits) could be used. In that case, numberof sets (pairs) is defined by number of combinations by pairs ofelectrodes.

It is to be understood that the preferred embodiment of FIG. 3 isillustrative. In particular, the scope of the present invention is notrestricted to circuitry in which voltage drops across the measurementcircuit and the reference circuits are measured explicitly, but ratherincludes all circuitry which accomplished the ends of the method of thepresent invention, using signals representative of the voltage dropsacross measurement circuit and the reference circuits respectively.

Referring to FIG. 4A-4B preferably not all measurement circuits could beused directly for characterizing Internal Thoracic Impedance (ITI) aswill be explained further below. For example, calculated internalimpedances corresponding only to the measurement circuits formed bypairs of uttermost electrodes of opposite arrays (101, 106) and(103,104) could be used. Values of seven internal impedancescorresponding to the rest measurement circuits including pairs ofelectrodes of opposite arrays are not calculated. However, impedance ofthese measurement circuits are used for calculating values of InternalThoracic Impedance (ITI) based on some physical assumptions as will beexplained further below.

Using of plurality of measured impedances corresponding to measurementcircuits performing measurements on different areas of lung couldimprove accuracy of measurements due to decreasing effect of possiblelocal non-uniformities or anomalies such as bullae within the lungs.Hence, during ITI monitoring (for a long period) the measurements couldbe performed periodically with replacement of measuring electrodes. Somedeviation in location of measuring electrodes could occur and in suchcases local non-uniformities or anomalies such as bullae could causesufficient variations of measurement results. Using a plurality ofelectrodes covering different areas of lung (with different currentways) and “averaging” obtained ITI measured results could reduce suchnegative effect caused by local non-uniformities or anomalies. Inaddition, multiple measurements used for calculating internalimpedance(s) also could improve accuracy of obtained result.

Turning back to FIG. 4A-4B the configuration and operation of the system10 of the invention is now more specifically exemplified, effectiveelectric circuit (circuitry) composed by plethysmography deviceelectrodes and biological object (skin/lung). Effective electric circuitis based on physical assumption that the total impedance measured acrosstwo electrodes placed on opposite sides of the biological object is thesum of two impedances: the impedance of the skin-electrode contacts andthe internal impedance of the body.

Generally the impedance Z_(M) of any measurement circuit formed by setof electrodes is the sum of the following impedances:Z _(M) =Z _(IN) +Z _(A) +Z _(B)  (A)Where:

-   -   Z_(IN)—the internal impedance of biological object (e.g. ITI);    -   Z_(A)—“transition” impedance which includes the impedance of        first electrode; the impedance of the skin-electrode contact of        electrode; and skin impedance;    -   Z_(B)—“transition” impedance which includes the impedance of        second electrode; the impedance of the skin-electrode contact of        electrode; and skin impedance.

On the other hand, the impedance of any reference circuit formed by setof electrodes is representative of “transition” impedances only, i.e.the sum of the following impedances:Z _(R) =Z _(A) +Z _(B)  (B),Where:

-   -   Z_(A)—“transition” impedance which includes the impedance of        first electrode; the impedance of the skin-electrode contact of        electrode; and skin impedance;    -   Z_(B)—“transition” impedance which includes the impedance of        second electrode; the impedance of the skin-electrode contact of        electrode; and skin impedance

Thus, internal impedance of biological object (e.g. ITI in our case)Z_(IN) could be calculated using voltage drops across measurement andreference circuits based on effective electric circuitry illustrated inFIG. 4A-4B At least two measurement circuits formed by sets comprisingelectrodes with substantially equal (similar) distance therebetween areused according to the present invention.

Measurement and reference circuits of the present invention could becharacterized by the following impedances:

-   -   Z₁—impedance of electrode and skin-electrode contact of        electrode 101;    -   Z₂—impedance of electrode and skin-electrode contact of        electrode 102;    -   Z₃—impedance of electrode and skin-electrode contact of        electrode 103;    -   Z₁₁—impedance of electrode and skin-electrode contact of        electrode 104;    -   Z₁₂—impedance of electrode and skin-electrode contact of        electrode 105;    -   Z₁₃—impedance of electrode and skin-electrode contact of        electrode 106;    -   Z₄—skin impedance between electrode 101 and 102; Z₅—skin        impedance between electrode 102 and 103;    -   Z₉—skin impedance between electrode 104 and 105;    -   And Z₁₀—skin impedance between electrode 105 and 106.

Sets of electrodes forming measurement circuits could comprise fromminimum two up to all electrodes of both groups of electrodes while setsof electrodes forming reference circuits could comprise from minimum twoand up to all electrodes of one of the groups of electrodes.

In order to be able calculate plurality (at least two) internalimpedances of biological object (e.g. ITI) appropriate number ofmeasurements by should be performed.

Reference is made to FIG. 5 exemplifying the effective electric circuit(circuitry) composed by plethysmography device electrodes and biologicalobject (skin/lung) according to preferred embodiment of the presentinvention. According to this embodiment each set of electrodes formingmeasurement and reference circuits comprise a pair of electrodes andnumber of sets (pairs) is defined by number of combinations by pairs ofall electrodes. For six electrode's scheme, e.g. used in Edema GuardMonitor (EGM) model RS-001 (RS Medical Monitoring, Israel) total numberof sets (pairs) is 15 and accordingly 15 measurement sessions providing15 values of impedance M₁-M₁₅ are performed. Each of measurement sessiondefines impendences of whether of measurement or reference circuitscalculated according to Ohm's Law based on the measured values ofvoltage drops. According to the present invention, internal impedanceZ_(in) of biological object (lung in the present example) could becalculated using the following 15 measured impedances M₁-M₁₅ of 15circuits formed by pairs of electrodes:Z ₁ +Z ₆ +Z ₁₁ =M ₁Z ₁ +Z ₄ +Z ₂ =M ₂Z ₂ +Z ₅ +Z ₃ =M ₃Z ₁ +Z ₄ +Z ₄ +Z ₃ =M ₄Z ₂ +Z ₇ +Z ₁₂ =M ₅Z ₃ +Z ₈ +Z ₁₃ =M ₆Z ₁₁ +Z ₉ +Z ₁₂ =M ₇Z ₁₂ +Z ₁₀ +Z ₁₃ =M ₈Z ₁₁ +Z ₉ +Z ₁₀ +Z ₁₃ =M ₉Z ₁ +Z ₁₄ +Z ₁₂ =M ₁₀Z ₂ +Z ₁₆ +Z ₁₁ =M ₁₁Z ₂ +Z ₁₅ +Z ₁₃ =M ₁₂Z ₃ +Z ₁₂ +Z ₁₂ =M ₁₃Z ₁ +Z ₁₉ +Z ₁₃ =M ₁₄Z ₁₁ +Z ₁₈ +Z ₃ =M ₁₅

Where in addition to impendences presented in FIG. 3 as described above,two additional impendences Z₁₈ and Z₁₉ are introduced being internalimpedances of biological object (e.g. ITI) corresponding to measurementcircuit composed by pairs of “uttermost” opposite electrodes (101,106)and (103,104).

According to the present invention totally 19 values of impedancesincluding impedances of electrodes and skin-electrode contacts and 9internal impedances of biological object (e.g. ITI) (Z₆, Z₇, Z₈, Z₁₄,Z₁₅, Z₁₆, Z₁₇, Z₁₈ and Z₁₉) could be obtained by solving a system of theabove 15 linear equations corresponding to 15 measurement sessions. Thefollowing physical assumption should be applied in order to be able toget 19 values from 15 linear equations: Z₆=Z₇=Z₈ and Z₁₄=Z₁₅=Z₁₆=Z₁₇.

In that case 19 values of impedances could be calculated as following:Z ₁=(2M ₁+2M ₂+2M ₃−2M ₄−2M ₅ +M ₁₀ −M ₁):2Z ₂=(M ₂ +M ₃ −M ₄):2Z ₃=(2M ₃ −M ₁₀+2M ₁+2M ₂+2M ₃−2M ₄−2M ₅ −M ₁₁):2Z ₄=(2M ₅−2M ₁ −M ₂−3M ₃+3M ₄ −M ₁₀ +M ₁₁):2Z ₅=(M ₁₀−2M ₁−3M ₂ −M ₃+3M ₄+2M ₅ +M ₁₁−2M ₁₃):2Z ₆ =Z ₇ =Z ₈Z ₇=(2M ₅ −M ₂ −M ₃ +M ₄ −M ₇ −M ₈ +M ₉):2Z ₉=(2M ₅ −M ₁₁ +M ₁₀−2M ₁ −M ₂ −M ₃ +M ₄−2M ₈+2M ₉):2Z ₁₀=(2M ₅−2M ₇+2M ₉−2M ₁₂ +M ₁₀−2M ₁ −M ₂ −M ₃ +M ₄ +M ₁₁):2Z ₁₁=(M ₁₁ −M ₁₀+2M ₁ +M ₂ +M ₃ −M ₄−2M ₅ +M ₇ +M ₈ −M ₉):2Z ₁₂=(M ₇ +M ₈ −M ₉):2Z ₁₃=(2M ₁₂ −M ₁₀ +M ₇ +M ₈ −M ₉+2M ₁ +M ₂ +M ₃ −M ₄−2M ₅ −M ₁₁):2Z ₁₄=(M ₁₀−2M ₁−2M ₂−2M ₃+2M ₄+2M ₅ +M ₁₁ −M ₇ −M ₉):2Z ₁₄ =Z ₁₅ =Z ₁₆ =Z ₁₇Z ₁₈=(2M ₁₄−4M ₁−3M ₂−3M ₃+3M ₄+4M ₅+2M ₁₁−2M ₁₂ −M ₇ −M ₈ +M ₉):2Z ₁₉=(2M ₁₅+2M ₁₀−4M ₁−3M ₂−3M ₃+3M ₄+4M ₅ −M ₇ −M ₈ +M ₉−2M ₁₃):2

Performing maximal possible number of measurements for multi-electrode(six—in the present example) system provides most efficient way ofsystem operation.

Preferably, only values of internal impedances Z₁₈ and Z₁₉ correspondingto measurement circuits defined by “uttermost” opposite electrodes couldbe calculated and used for characterizing internal impedance of thebiological object (e.g. ITI). Since the inter-electrodes space in thatcase covers maximum biological object (e.g. lung) tissue thesemeasurements could be most representative of variations of liquid amountwithin the lung tissue.

Combing (e.g. averaging) of calculated values internal impedances Z₁₈and Z₁₉ could sufficiently improve accuracy of measurements by furtherdecreasing affecting of possible local non-uniformities or anomalieswithin the lungs.

The inventors have found that internal impedance of biological objectZ₁₈ and Z₁₉ (lung in the present example) could be calculated based onassumption that ITI corresponding to measurement circuits with similardistance between electrodes have substantially the close values.

To this end, impedances Z₆, Z₇ and Z₈ corresponding to measurementcircuits comprising opposite electrodes, such as first outer electrodes101-104, internal electrodes 102-105 and second outer electrodes 103-106are considered as having substantially the same values:Z ₆ =Z ₇ =Z ₈

Also internal impedances Z₁₄, Z₁₅, Z₁₆ and Z₁₇ are considered as havingsubstantially the same values:Z ₁₄ =Z ₁₅ =Z ₁₆ =Z ₁₇

If lung tissue does not include heterogeneous structures and ishomogenous on the pass of electromagnetic signals, internal impedancesZ₆, Z₇, Z₈ as well Z₁₄, Z₁₅, Z₁₆, Z₁₇ will have substantially equalvalues. In that case, accuracy of calculated internal impedances Z₁₈ andZ₁₉ will increase due to performing maximal possible number ofmeasurements.

When lung tissue includes heterogeneous structures within the pass ofelectromagnetic signal between at least one pair of electrodes, therecould be some difference between the values of internal impedances in atleast one of the groups Z₆, Z₇, Z₈ and Z₁₄, Z₁₅, Z₁₆ Z₁₇. In such casevalue of internal impedances used for calculating will be effectively“averaged” and effect of heterogeneous structures on calculatedimpedances Z₁₈ and Z₁₉ will be decrease.

According to another preferred embodiment, In order to provide even moreaccurate measurements, calculated values of Z₁₈ and Z₁₉ could becompared therebetween.

Since the measurements are performed on live non-static biologicalobject, e.g. human patient, various parts of breath cycle, un-controlledmovements etc. could cause substantial changes of measurementconditions. Such changes could affect obtained values of internalimpedances and decrease accuracy of final calculated result. To thisend, pre-set value of difference between Z₁₈ and Z₁₉ could be used formeasurements verification. Such pre-set value typically could beselected not exceeding 3 Ohms.

In case when difference between values of Z₁₈ and Z₁₉ does not exceeded(is less) pre-set value such measurement session(s) will be accepted andcalculated values Z₁₈ and Z₁₉ could be used for diagnostic purposes.

Additionally, averaging of calculated values Z₁₈ and Z₁₉ could beperformed.

Contrary, in case when difference between values of Z₁₈ and Z₁₉ doesincrease pre-set value such measurement session(s) will be rejected ordiscarded. Further, measurement session(s) could be repeated tillacceptable result will be obtained as described above.

Appropriate utility of control unit (e.g. control unit 306 of FIG. 6 )could be provided enabling comparing of calculated values of internalimpedance of biological object (e.g. ITI) and performing additionalmeasurement sessions. In addition, inputting and storing of theabove-mentioned pre-set value could be performed using appropriateInput/Output interface—IOI and data storage unit.

The calculation of the actual impedance values of the skin-electrodecontacts of electrodes 101 106 enables to carry out long-term monitoringof the electrical impedance of a biological object with compensation forskin-electrode resistance drifts, even when the impedance values of theskin-electrode contacts are substantially different.

Reference is made to FIG. 5 exemplifying the configuration of system 100of the present invention specifically useful for impedanceplethysmography. As shown in FIG. 5 system 100 according to the presentinvention preferably includes: current source 300; analog multiplexer302 for alternately connecting current source 300 to predetermined setof electrodes forming whether measurement or reference electricalcircuits; a voltage measurement unit 304; a control unit 306 thatincludes data processing utility 308 for carrying out calculations; adata-storage unit (memory) 310 for storing data during the measurementsessions and monitoring period; a controller utility 312 for controllingthe operation of units of system 100 such as current source 300, analogmultiplexer 302, voltage measurement unit 304, etc.; data Input/Outputinterface—IOI 314. Data IOI 314 could include appropriate buttons,display, touch-screen enabling input of commands, data, etc. foroperating the system 100 and displaying operating status of the systemand measurement data. An alarm unit also could be provided (not-shown)

Data processing utility 308 could comprise appropriate SW and HW that isconnectable to data-storage unit 310, data IOI 315 and optionally toalarm unit. These SW and HW provide operation of system 100 according tothe method described above.

System 100 could be powered from external (e.g. AC) and/or internal(e.g. battery) sources by means of a power supply (not shown).

Voltage measurement unit 304 typically includes rectifier (not shown)for obtaining the absolute value of the signals representing the voltagedrops and analog to digital A/D converter for converting analog signalsto a digital form signal compatible with data processing utility 308.

When using a device according to the present invention, electricalsource 300 is alternately connected to each of the electrical circuitsformed by pre-determined sets of electrodes 101-106 shown in FIG. 5 bymeans of analog multiplexer (commutator) 302. Signal representing thevoltage drop of a specific electrical circuit is fed voltage measurementunit 304 which preferably provides signal in digital form. The obtaineddigital signal is fed into control unit 306 for storing in data-storageunit (memory) 310 for further processing by data processing utility 308.

Control unit 306 orders analog multiplexer (commutator) 302 to formpre-determined number and configurations of measurement and referencecircuits, e.g. 15 for six-electrodes scheme with two-electrodes sets ofelectrodes.

After data-storage unit (memory) 310 has received data from each ofelectrical circuits, data processing utility 308 can calculate theinternal impedances Z_(IN) (values of Z₁₈ and Z₁₉) according to themethod described above. Data processing utility 308 also could performadditional processing of multiple measurement results, e.g. comparisonof values of Z₁₈ and Z₁₉ and their combining due to pre-set algorithm(averaging, weighing, etc.).

Preferably, when performing a monitoring of a biological object theprocess described above is carried out periodically, so that Dataprocessing utility 308 can simultaneously calculate the values of theinternal impedance Z_(IN) as well as changes therein. The change inZ_(IN) may be calculated, for example, as the difference between thelast value and the initial or previously measured value(s) or as apercentage therefrom. The results of the calculations could betransmitted to data IOI interface 14 and displayed by internal orexternal display, to data-storage unit (memory) 310, and to optionalalarm unit.

In the event that the value of Z_(IN) has decreased below a criticalvalue, and/or in the event that the change in Z_(IN) has exceeded acritical value, the alarm could be activated.

Data-storage unit (memory) 310 may provide data for analysis during themonitoring period so as to monitor the progress of the disease.

Thus, the present invention provides an effective and reliable techniquefor measuring the internal electrical impedance of a biological objectand specifically Transthoracic impedance which can be used for effectivemonitoring in time of lung liquid volume status.

Those skilled in the art will readily appreciate that variousmodifications and changes can be applied to the embodiments of theinvention hereinbefore described without departing from its scopedefined in and by the appended claims.

The invention claimed is:
 1. A method for multi-electrode monitoring ofan internal electrical impedance of a biological object, the methodcomprising the steps of: i) placing a first array of electrodes on oneside of the biological object and a second array of electrodes on anopposite side of the biological object, wherein each of said arrayscomprises at least three spaced apart electrodes; ii) performing aplurality of measurements on different pairs of electrodes that comprisetwo or more opposite sides electrode pairs, wherein each of saidmeasurements is performed on a different pair of said electrodes byapplying an alternating electrical current between the electrodes of thepair and obtaining voltage signals representative of a voltage dropthereon; wherein each opposite sides electrode pair comprises anelectrode of the first array and an electrode of the second array; iii)calculating, for each electrode (of the different pairs of electrodes),values of impedance(s) indicative of sums of electrode impedance and askin-electrode contact impedance to provide multiple values; whereinsaid calculating comprises using a system of linear equations; iv)comparing said calculated sums to each other, wherein a differencebetween sums, found by the comparing, that exceeds a predeterminedthreshold value is representative of a potential failure in at least oneof said electrodes related to the sums; v) calculating an internalelectrical impedance value of the biological object based on (a)measurements of at least two opposite sides electrode pairs of the twoor more opposite sides electrode pairs, and (b) calculated sums for eachelectrode of the at least two opposite sides electrode pairs; andwherein the method comprising performing measurement sessions byrepeating steps ii)-v) when the result of the comparison exceeds thepredetermined threshold value.
 2. The method of claim 1 furthercomprising defining a correctness of one or more measurements obtainedduring the measurement sessions or a faultlessness of at least one ofthe electrodes based on said result of the comparing.
 3. The method ofclaim 2 further comprising denying acceptance of the measurementsessions.
 4. The method of claim 2 further comprising replacing anyfaulty electrode.
 5. The method of claim 1 wherein said biologicalobject includes a human body.
 6. The method according to claim 1 whereinsaid predetermined threshold value is 150 Ohm.
 7. The method accordingto claim 1 wherein said internal electrical impedance of the biologicalobject includes an Internal Thoracic Impedance (ITI).
 8. The methodaccording to claim 7 wherein said alternating electrical current has avalue from 0.5 to 5 mA.
 9. The method of claim 8 wherein saidalternating electrical current has a value from 1 to 2 mA.
 10. Themethod according to claim 8 wherein said alternating electrical currenthas a frequency from 50 to 200 KHz.
 11. The method of claim 8 whereinsaid alternating electrical current includes alternating current of anyperiodic waveform.
 12. The method of claim 7 wherein a number of saidapplying is defined by number of combinations by said pairs ofelectrodes.
 13. The method according to claim 1 wherein the two or moreopposite sides electrode pairs comprises any combination between anyelectrode of the first array and any electrode of the second array. 14.The method according to claim 1 wherein the two or more opposite sideselectrode pairs comprises only some of any combination between anyelectrode of the first array and any electrode of the second array. 15.The method according to claim 1 wherein the calculating of the internalelectrical impedance value comprises averaging the measurements of theat least two opposite sides electrode pairs.
 16. The method according toclaim 1 wherein the calculating of the internal electrical impedancevalue comprises combining the measurements of the at least two oppositesides electrode pairs by using a pre-set algorithm.
 17. The methodaccording to claim 1 wherein biological object is a lung and wherein thecalculating of the internal electrical impedance value comprisescombining the measurements of the at least two opposite sides electrodepairs by using a pre-set algorithm.
 18. The method according to claim 1wherein a number of the linear equations is smaller than a number of theplurality of measurements.
 19. The method according to claim 1 whereinthe calculating using the system of linear equations is based on anassumption that internal impedances of equal-length paths within thebiological object are equal to each other.
 20. A method formulti-electrode monitoring of an internal electrical impedance of abiological object, the method comprising the steps of: i) placing afirst array of electrodes on one side of the biological object and asecond array of electrodes on an opposite side of the biological object,wherein each of said arrays comprises at least three spaced apartelectrodes; ii) performing a plurality of measurements on differentpairs of electrodes that comprise two or more opposite sides electrodepairs, wherein each of said measurements is performed on a differentpair of said electrodes by applying an alternating electrical currentbetween the electrodes of the pair and obtaining voltage signalsrepresentative of a voltage drop thereon; wherein each opposite sideselectrode pair comprises an electrode of the first array and anelectrode of the second array; iii) calculating, for each electrode (ofthe different pairs of electrodes), values of impedance(s) indicative ofsums of electrode impedance and a skin-electrode contact impedance toprovide multiple values; wherein said calculating comprises using asystem of linear equations based on an assumption that internalimpedances of equal-length paths within the biological object are equalto each other; iv) comparing said calculated sums to each other, whereina difference between sums, found by the comparing, that exceeds apredetermined threshold value is representative of a potential failurein at least one of said electrodes related to the sums; and v)calculating an internal electrical impedance value of the biologicalobject based on (a) measurements of at least two opposite sideselectrode pairs of the two or more opposite sides electrode pairs, and(b) calculated sums for each electrode of the at least two oppositesides electrode pairs.